Huntingtons's Disease (HD) is an autosomal dominant neurological disorder caused by the inheritance of a CAG repeat greater than 36 in length in exon 1 of a gene of unknown function, huntingtin [1,2]. There is no known cure for this lethal neurological disorder, however, progress has been made in identifying candidate processes and in the development high-throughput screens to identify potential therapeutics. The broad long term goal of this project is to help design tools to aid in therapeutic discovery for HD. An important tool in testing the efficacy of therapeutic candidates is an animal model that accurately replicates the molecular pathology of HD. Knock-in mouse models of HD currently have the greatest potential for accurately mimicking the disease, but have a phenotype so mild that experimental testing of therapeutics in these models would presently be difficult. The goals of this proposal are to 1) determine whether increasing the repeat length of a knock-in HD mouse model will overcome this difficulty, 2) to provide the field with a panel of HD knock-ins with different repeat lengths (100,150, 200 and 250 CAGs) congenic to two different inbred mouse lines (C57Bl/6 and CBA), 3) to provide reliable baseline [phenotype information to researchers interested in testing potential therapeutics. [unreadable] [unreadable] [unreadable]